Table 2.

Basal and induced behavioral analysis of RGS9-manipulated animals^a

Behavior	Animal model	Manipulation	Treatment	Behavioral test	Behavioral phenotype relative to control	Refs
Coordination or cognition
Gross motor coordination	RGS9KO mice	None	None	Accelerating rotarod	Deficits in motor coordination; similar rate of acute motor learning	[26]
			None	Locomotor activity	Similar horizontal locomotor activity	[26]
Emotional behaviors	RGS9KO mice	None	None	Fear conditioning	Similar context and cue-dependent fear conditioning	[26]
			None	Open field	Similar anxiety-like behavior	[26]
			None	Pre-pulse inhibition	Similar sensory motor gating	[26]
			None	Shock threshold	Similar startle amplitude	[26]
Motor behavior
Locomotor response to dopamine-receptor agonists	Rats	Unilateral HSV–RGS9-2 (versus HSV–LacZ) overexpression in the NAc	Acute apomorphine (dopamine-receptor agonist)	Circling and rotation recording	↑ ↑b Rotational bias towards the side of overexpression	[23]
			Acute quinpirole (D2-receptor agonist)	Circling and rotation recording	↑ Rotational bias towards the side of overexpression	[23]
			Acute SKF81297 (D1-receptor agonist)	Circling and rotation recording	No rotational bias	[23]
Antipsychotic drug-induced dyskinesia	RGS9KO mice	None	Acute apomorphine, or quinpirole or SKF38393	AIM recording	Similar induction of few AIMs	[24]
			3 days reserpine	AIM recording	Similar loss of AIMs	[24]
	RGS9KO mice	Reserpinized- or haloperidol- treated animals (3 days)	Acute apomorphine	Locomotor activity assay	↑ Locomotor activity	[24]
			Acute quinpirole or SKF38393	Locomotor activity	Similar locomotor activity	[24]
			Acute quinpirole or apomorphine	AIM recording	↑ ↑ AIM score	[24]
			Acute SKF38393	AIM recording	Unchangeable AIM score	[24]
L-dopa-induced dyskinesia in Parkinson’s disease	Rats; unilaterally 6- OHDA-lesioned parkinsonian under L-dopa and benserazide treatment	HSV–RGS9-2 (versus HSV–LacZ) overexpression in the striatum	None	AIM recording	↓ Dyskinesia	[33]
	Monkeys Macaca fascicularis; MPTP and dyskinetic (parkinsonian under Modoparc- treatment-induced dyskinesia)	HSV–RGS9-2 (versus HSV–LacZ) overexpression in the striatum	None	Parkinsonian monkey rating scale	Similar PD score (antiparkinsonian action of Modopar)	[33]
			None	Dyskinesia disability scale	↓ LID	[33]
			None	Locomotor activity assay	↓ Locomotor activity	[33]
			Acute ropinirole (D2-receptor and D3-receptor agonist)	Parkinsonian monkey rating scale	↓ PD score (↓ antiparkinsonian action of Modopar)	[33]
			Acute ropinirole	Dyskinesia disability scale	↓ LID	[33]
			Acute ropinirole	Locomotor activity assay	↓ Locomotor activity	[33]
	RGS9KO mice	Unilateral 6-OHDA lesion-induced PD	Chronic L-dopa and benserazide treatment	Rotational and locomotor recording	Similar rotational behavior (antiparkinsonian effect)	[33]
			Chronic L-dopa and benserazide treatment	AIM rating scale	↑ Forelimb and axial AIM (dyskinesia)	[33]
Response to psychostimulants	RGS9KO mice	None	Acute amphetamine (low dose)	Locomotor activity	↑ Locomotor activity	[23]
			Acute amphetamine (high dose)	Locomotor activity	Similar locomotor activity	[23]
			Acute cocaine	Locomotor activity	Similar locomotor activity	[23]
			Chronic cocaine	Locomotor activity	↑ Locomotor activity	[23]
	Rats	Bilateral HSV-RGS9-2 (versus HSV-LacZ) overexpression in the NAc	Acute cocaine (low dose)	Locomotor activity	↓ Locomotor activity	[23]
			Acute cocaine (high dose)	Locomotor activity	Similar locomotor activity	[23]
Antinociception
Acute	RGS9KO mice	None	Acute morphine	Hot plate	↑ Supra-spinal-cord-mediated analgesia	[25]
			Acute morphine	Tail flick	↑ Spinal-cord-mediated analgesia	[25]
Tolerance	RGS9KO mice	None	Chronic morphine	Hot plate	Delayed tolerance development	[25]
		SNI model of neuropathic pain	Chronic morphine	Von Frey	Delayed tolerance development	Zachariou, V., unpublished
Reward
	RGS9KO mice	None	Cocaine (low dose)	CPP	↑ Place conditioning	[23,25]
			Cocaine (high dose)	CPP	Similar place conditioning	None
			Morphine (low dose 0.5–3 mg/kg)	CPP test	↑ Place conditioning (decreased threshold)	[23,25]
Physical dependence and withdrawal
	RGS9KO mice	Morphine dependence (treatment with escalating morphine doses)	Acute naloxone	Withdrawal test	↑ Opiate withdrawal	[25]

^aAbbreviations: AIM, arbitrary involuntary movement; CPP, conditioned place preference; HSV, herpes simplex virus; LacZ, β galactosidase; LID, L-dopa-induced dyskinesia; 6-OHDA, 6-hydroxydopamine; PD, Parkinson’s disease; SNI, spared nerve injury.

^bArrows denote a decrease or increase in behavior compared with control animals.

^cModopar is L-dopa plus carbidopa.